DX9065a, an Xa inhibitor, inhibits prothrombin-induced A549 lung adenocarcinoma cell proliferation.
In this study we demonstrate that prothrombin activates the cell proliferation of the lung adenocarcinoma A549 cells. The A549 cell expresses factor Xa-like prothrombinase activity on its surface and prothrombin was converted to thrombin on the cell surface. Furthermore, thrombin induced the activation of PKC, increased [Ca2+]i and potentiated MAP kinase activity through thrombin receptor. The mitogenic activity of prothrombin and the conversion to thrombin were completely abolished by the synthetic coagulation factor Xa inhibitor, DX9065a. These findings suggest that DX9065a is an effective agent for a therapeutic strategy against cancer itself and prothrombotic complications associated with malignancy.
Nakata
M
M
Department of Laboratory Medicine, Kagoshima University School of Medicine, Japan. nakata@khosp2.kufm.kagoshima-u.ac.jp
Kanekura
S
S
Maruyama
I
I
D000230:Adenocarcinoma / Q000473:pathology; D000925:Anticoagulants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D065427:Factor Xa Inhibitors; D006801:Humans; D009281:Naphthalenes / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011516:Prothrombin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009281:Naphthalenes; D011422:Propionates; D011516:Prothrombin; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium